AsianScientist (Sep. 2, 2019) – An international team of scientists has developed a technique to reprogram mature cells into totipotent stem cells—that is, cells that have the ability to become all other cell types in the body. Their finding are published in the journal Stem Cell Reports.
After an egg is fertilized, it begins to divide and passes through several stages. Cells in the two-cell stage are totipotent. After many more cell divisions, the embryo turns into a blastocyst that is implanted in the womb, where it differentiates and grows into a fetus. A blastocyst is like an almost hollow ball. The outer shell of the ball is made from trophoblasts—cells that eventually form the placenta, while the cells inside are pluripotent cells—cells that can become any type of cell in the body, but not the placenta.
For several years, scientists have been able to convert mature cells such as skin cells into pluripotent cells but not totipotent cells. In this study, scientists led by Dr. Cody Kime at RIKEN, Japan, with colleagues in the US, found a way to return mature cells to a state resembling that of a two-cell embryo. They did so by treating mature cells with natural molecules found in the early mouse embryo: bone morphogenetic protein 4, leukemia inhibitory factor, lysophosphatidic acid, and ascorbic acid.
After seven days, the researchers observed 5-30 floating self-assembled blastocyst-like structures in culture. Examining small clusters of cells a few days before the blastocyst-like structures appeared, the team found that the cells expressed genes for totipotency.
Next the group investigated how genetically and functionally similar their blastocyst-like structures were to actual blastocysts. They observed similar patterns of gene expression, but at lower-than-natural levels, indicating that the new technique does not perfectly reproduce blastocysts. Nevertheless, when transplanted to the womb of pseudo-pregnant mice, the blastocyst-like structures often induced changes to the uterus that are necessary for successful blastocyst implantation, including the integration of the maternal blood supply.
The implanted structures often grew and produced many types of cells that resembled those naturally found in early developing embryos. Eventually, the embryos were resorbed, and the surrounding tissue showed signs that were similar to instances of natural resorption.
“Totipotency is the highest order of cell potency: one totipotent cell can form the placenta and the body,” said Kime. “If our system can be improved to fully reach that state, we will be able to improve basic research in the fields of embryogenesis and fertility, as well as basic and clinical research in regenerative medicine.”
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